Correlation between carbohydrate and catecholamine level impairments in methionine sulfoximine epileptogenic rat brain.
This work shows that the convulsant methionine sulfoximine induces an increase in glucose and glycogen levels and a parallel decrease in norepinephrine and dopamine levels in rat brain. Among the epileptogenic agents, methionine sulfoximine is known to have a glycogenic property in the central nervous system. The aim of this work is to look for the neurochemical mechanism underlying this property. For this, catecholamines, glucose, and glycogen were measured at the same time in different areas of the brain in rats submitted to methionine sulfoximine. The convulsant induced an increase in glucose and glycogen levels as previously described and a decrease in dopamine and norepinephrine levels in all the areas of the rat brain. These changes were roughly dose dependent. When L-dihydroxyphenylalanine and benserazide (a decarboxylase inhibitor) were administered with methionine sulfoximine, the latter failed to induce seizures in rat up to 8 h after dosing. Moreover, the glucose and glycogen amounts did not increase. In all these experiments, there was an obvious evidence of parallelism between seizures, increase in carbohydrate levels, and decrease in catecholamine levels. These results allow to conclude that the glycogenic property of methionine sulfoximine in the central nervous system probably results from its ability to decrease norepinephrine and dopamine levels. Because the effect of the convulsant on the catecholamine levels persisted for long, it is normal that glucose and glycogen levels increased during preconvulsive, convulsive and postconvulsive period. Methionine sulfoximine is probably glycogenic in rat brain because it decreases catecholamine levels for a long time.
Hevor
T K
TK
Laboratoire de Neurobiologie Fonctionnelle, Université des Sciences et Techniques de Lille Flandres-Artois, Villeneuve d'Ascq, France.
Aissi
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Delorme
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P
D000818:Animals; D001545:Benserazide / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D050260:Carbohydrate Metabolism; D002395:Catecholamines / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D008717:Methionine Sulfoximine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D002395:Catecholamines; D008717:Methionine Sulfoximine; D007980:Levodopa; D001545:Benserazide; D006003:Glycogen; D005947:Glucose; D004298:Dopamine; D009638:Norepinephrine